tbuckley/cabot-search huggingface dataset:
Associations between Per- and Polyfluoroalkyl Substances Exposures and Blood Lipid Levels among Adults—A Meta-Analysis
Authors: Binkai Liu, Lu Zhu, Molin Wang, Qi Sun
Journal: Environmental Health Perspectives (2023)

Associations between per- and polyfluoroalkyl substances (PFAS) and blood lipid levels in humans were mixed.The objective of this meta-analysis was to summarize associations between PFAS and blood lipids in adults.A literature search was conducted on PubMed and Web of Science for articles published through 13 May 2022 that examined associations between PFAS and blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triacylglycerols (TGs). Inclusion criteria included the presence of associations between five PFAS (PFOA, PFOS, PFHxS, PFDA, and PFNA) and four blood lipid measures (TC, HDL-C, LDL-C, and TGs) in adults. Data on study characteristics and PFAS-lipid associations were extracted. Assessments of individual study quality were performed. Associations of changes of blood lipid levels corresponding to 1 interquartile range (IQR)-unit increase of blood PFAS levels were pooled using random effects models. Dose-response relationships were examined.Twenty-nine publications were included in the present analyses. Every IQR increase of PFOA was significantly associated with a 2.1-mg/dL increase in TC (95% CI: 1.2, 3.0), a 1.3-mg/dL increase in TGs (95% CI: 0.1, 2.4), and a 1.4-mg/dL increase in LDL-C (95% CI: 0.6, 2.2). PFOS was also significantly associated with TC and LDL-C levels, and the corresponding values were 2.6 (95% CI: 1.5, 3.6) and 1.9 (95% CI: 0.9, 3.0), respectively. Associations of PFOS and PFOA with HDL-C levels were largely null. For minor PFAS species, PFHxS was significantly associated with higher levels of HDL-C [0.8 (95% CI: 0.5, 1.2)]. Inverse associations were observed between PFDA and TGs [-5.0 (95% CI: -8.1, -1.9)] and between PFNA and TGs [-1.7 (95% CI: -3.5, -0.02)], whereas a positive association was observed between PFDA and HDL-C [1.4 (95% CI: 0.1, 2.7)]. Nonsignificant nonlinear dose-response relationships were identified for associations of PFOA and PFOS with certain blood lipids.PFOA and PFOS were significantly associated with TC and LDL-C levels in adults. Whether these findings may translate into an elevated cardiovascular disease risk associated with PFAS exposure warrants further investigation. https://doi.org/10.1289/EHP11840.
Bayesian prediction-based individualized dosing of anti-methicillin-resistant Staphylococcus aureus treatment: Recent advancements and prospects in therapeutic drug monitoring
Authors: Kazutaka Oda, Hideyuki Saito, Hirofumi Jono
Journal: Pharmacology & Therapeutics (2023)

As one of the efficient techniques for TDM, the population pharmacokinetic (popPK) model approach for dose individualization has been developed due to the rapidly growing innovative progress in computer technology and has recently been considered as a part of model-informed precision dosing (MIPD). Initial dose individualization and measurement followed by maximum a posteriori (MAP)-Bayesian prediction using a popPK model are the most classical and widely used approach among a class of MIPD strategies. MAP-Bayesian prediction offers the possibility of dose optimization based on measurement even before reaching a pharmacokinetically steady state, such as in an emergency, especially for infectious diseases requiring urgent antimicrobial treatment. As the pharmacokinetic processes in critically ill patients are affected and highly variable due to pathophysiological disturbances, the advantages offered by the popPK model approach make it highly recommended and required for effective and appropriate antimicrobial treatment. In this review, we focus on novel insights and beneficial aspects of the popPK model approach, especially in the treatment of infectious diseases with anti-methicillin-resistant Staphylococcus aureus agents represented by vancomycin, and discuss the recent advancements and prospects in TDM practice.
Persistent alveolar inflammatory response in critically ill patients with COVID-19 is associated with mortality
Authors: Justin de Brabander, Leonoor S Boers, Robert F J Kullberg, Shiqi Zhang, Esther J Nossent, Leo M A Heunks, Alexander P J Vlaar, Peter I Bonta, Marcus J Schultz, Tom van der Poll, JanWillem Duitman, Lieuwe D J Bos
Journal: Thorax (2023)

Patients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response.In this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar-plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients.284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels.Patients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.
Nasal stimulation with l-menthol ameliorates breathlessness in patients with interstitial lung disease
Authors: Masashi Kanezaki, Kunihiko Terada, Satoru Ebihara
Journal: European Respiratory Journal (2023)

<b>Olfactory stimulation with l-menthol may be a safe and effective treatment in patients with interstitial lung disease. It significantly decreases breathing discomfort, air hunger, and breathing effort during inspiratory resistive loaded breathing.</b>https://bit.ly/40KQ0Ns
High rate of early HEV seroconversion after liver transplantation among cirrhotic patients: Should we test for it?
Authors: Alessandra Mazzola, Eve Todesco, Shadia Ali, Mathilde Bastide, Frederic Charlotte, Philippe Flandre, Sophie Sayon, Melanie Houot, Vincent Calvez, Dominique Thabut, Olivier Scatton, Anne-Geneviève Marcelin, Filomena Conti
Journal: Journal of Infection (2023)
An eosinophil peroxidase activity assay accurately predicts eosinophilic chronic rhinosinusitis
Authors: Kristine A. Smith, Amarbir S. Gill, Chelsea E. Pollard, Jorgen S. Sumsion, Hedieh Saffari, Shaelene Ashby, Benjamin L. Witt, Paige A. Shipman, David A. Gabrielsen, Michael T. Yim, Joshua M. Levy, Gretchen M. Oakley, Richard R. Orlandi, Gerald J. Gleich, Jeremiah A. Alt, Abigail Pulsipher
Journal: Journal of Allergy and Clinical Immunology (2023)
Challenges of evidence-informed offshore decommissioning: an environmental perspective
Authors: Anaëlle J. Lemasson, Paul J. Somerfield, Michaela Schratzberger, Antony M. Knights
Journal: Trends in Ecology & Evolution (2023)

Many offshore artificial structures are at or nearing their ends of life, and society faces the considerable challenge that is decommissioning. Current scientific evidence of the ecological and environmental consequences of decommissioning is insufficient to reliably and accurately inform decision-making and policy development. Thus, we must strengthen the scientific basis for evidence-informed decommissioning.
Molecular mechanisms underlying transformation of large granular lymphocytic leukemia to high-grade T-cell lymphoma
Authors: Cédric Pastoret, Francisco Llamas-Gutierrez, Maxime Fouchard, Aline Moignet, Marie-Laure Boulland, Philippe Gaulard, Roch Houot, Mikael Roussel, Thierry Fest, Thierry Lamy, Tony Marchand
Journal: Leukemia (2023)
A transformable nanoplatform with multiple therapeutic and immunostimulatory properties for treatment of advanced cancers
Authors: Xiangdong Xue, Haijing Qu, Ruonan Bo, Dalin Zhang, Zheng Zhu, Bai Xiang, Longmeng Li, Marina Ricci, Chong-Xian Pan, Tzu-Yin Lin, Yuanpei Li
Journal: Biomaterials (2023)
Society News
Journal: Neuro-Oncology (2023)

Journal Article Society News Get access Neuro-Oncology, Volume 25, Issue 5, May 2023, Page 1013, https://doi.org/10.1093/neuonc/noad061 Published: 04 May 2023 Article history Corrected and typeset: 04 May 2023 Published: 04 May 2023
Cross-Frequency Coupling and Intelligent Neuromodulation
Authors: Chien-Hung Yeh, Chuting Zhang, Wenbin Shi, Men-Tzung Lo, Gerd Tinkhauser, Ashwini Oswal
Journal: Cyborg and Bionic Systems (2023)

Cross-frequency coupling (CFC) reflects (nonlinear) interactions between signals of different frequencies. Evidence from both patient and healthy participant studies suggests that CFC plays an essential role in neuronal computation, interregional interaction, and disease pathophysiology. The present review discusses methodological advances and challenges in the computation of CFC with particular emphasis on potential solutions to spurious coupling, inferring intrinsic rhythms in a targeted frequency band, and causal interferences. We specifically focus on the literature exploring CFC in the context of cognition/memory tasks, sleep, and neurological disorders, such as Alzheimer's disease, epilepsy, and Parkinson's disease. Furthermore, we highlight the implication of CFC in the context and for the optimization of invasive and noninvasive neuromodulation and rehabilitation. Mainly, CFC could support advancing the understanding of the neurophysiology of cognition and motor control, serve as a biomarker for disease symptoms, and leverage the optimization of therapeutic interventions, e.g., closed-loop brain stimulation. Despite the evident advantages of CFC as an investigative and translational tool in neuroscience, further methodological improvements are required to facilitate practical and correct use in cyborg and bionic systems in the field.
Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)
Authors: Evangelos Terpos, Pellegrino Musto, Monika Engelhardt, Michel Delforge, Gordon Cook, Francesca Gay, Niels W. C. J. van de Donk, Ioannis Ntanasis-Stathopoulos, Annette Juul Vangsted, Christoph Driessen, Fredrik Schjesvold, Claudio Cerchione, Sonja Zweegman, Roman Hajek, Philippe Moreau, Hermann Einsele, Jesus San-Miguel, Mario Boccadoro, Meletios A. Dimopoulos, Pieter Sonneveld, Heinz Ludwig
Journal: Leukemia (2023)
Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population
Authors: Isabelle A. van Zeventer, Aniek O. de Graaf, Jonas B. Salzbrunn, Ilja M. Nolte, Priscilla Kamphuis, Avinash Dinmohamed, Bert A. van der Reijden, Jan Jacob Schuringa, Joop H. Jansen, Gerwin Huls
Journal: Cancer Cell (2023)
The mitochondrial unfolded protein response regulates hippocampal neural stem cell aging
Authors: Chih-Ling Wang, Rika Ohkubo, Wei-Chieh Mu, Wei Chen, Jiang Lan Fan, Zehan Song, Ayane Maruichi, Peter H. Sudmant, Angela O. Pisco, Dena B. Dubal, Na Ji, Danica Chen
Journal: Cell Metabolism (2023)
A chemically inducible IL-2 receptor signaling complex allows for effective in vitro and in vivo selection of engineered CD4+ T cells
Authors: Peter J. Cook, Su Jung Yang, Gene I. Uenishi, Annaiz Grimm, Samuel E. West, Li-Jie Wang, Chester Jacobs, Andrea Repele, Travis Drow, Ahmad Boukhris, Noelle P. Dahl, Karen Sommer, Andrew M. Scharenberg, David J. Rawlings
Journal: Molecular Therapy (2023)

Engineered T cells represent an emerging therapeutic modality. However, complex engineering strategies can present a challenge for enriching and expanding therapeutic cells at clinical scale. In addition, lack of in vivo cytokine support can lead to poor engraftment of transferred T cells, including regulatory T cells (T
Impact of PNPLA3 rs738409 Polymorphism on the Development of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease
Authors: Chiara Rosso, Gian Paolo Caviglia, Giovanni Birolo, Angelo Armandi, Grazia Pennisi, Serena Pelusi, Ramy Younes, Antonio Liguori, Nuria Perez-Diaz-del-Campo, Aurora Nicolosi, Olivier Govaere, Gabriele Castelnuovo, Antonella Olivero, Maria Lorena Abate, Davide Giuseppe Ribaldone, Piero Fariselli, Luca Valenti, Luca Miele, Salvatore Petta, Manuel Romero-Gomez, Quentin M. Anstee, Elisabetta Bugianesi
Journal: Clinical Gastroenterology and Hepatology (2023)
EZH2 inhibition remodels the inflammatory senescence-associated secretory phenotype to potentiate pancreatic cancer immune surveillance
Authors: Loretah Chibaya, Katherine C Murphy, Kelly D DeMarco, Sneha Gopalan, Haibo Liu, Chaitanya N Parikh, Yvette Lopez-Diaz, Melissa Faulkner, Junhui Li, John P Morris, Yu-Jui Ho, Sachliv K Chana, Janelle Simon, Wei Luan, Amanda Kulick, Elisa de Stanchina, Karl Simin, Lihua Julie Zhu, Thomas G Fazzio, Scott W Lowe, Marcus Ruscetti
Journal: Nature Cancer (2023)
An automated histological classification system for precision diagnostics of kidney allografts
Authors: Daniel Yoo, Valentin Goutaudier, Gillian Divard, Juliette Gueguen, Brad C. Astor, Olivier Aubert, Marc Raynaud, Zeynep Demir, Julien Hogan, Patricia Weng, Jodi Smith, Rouba Garro, Bradley A. Warady, Rima S. Zahr, Marta Sablik, Katherine Twombley, Lionel Couzi, Thierry Berney, Olivia Boyer, Jean-Paul Duong-Van-Huyen, Magali Giral, Alaa Alsadi, Pierre A. Gourraud, Emmanuel Morelon, Moglie Le Quintrec, Sophie Brouard, Christophe Legendre, Dany Anglicheau, Jean Villard, Weixiong Zhong, Nassim Kamar, Oriol Bestard, Arjang Djamali, Klemens Budde, Mark Haas, Carmen Lefaucheur, Marion Rabant, Alexandre Loupy
Journal: Nature Medicine (2023)
Patients’ perceptions on clinical trials outcomes in pulmonary arterial hypertension therapy
Authors: Vicky Mai, Camille Gosselin, Élodie Tremblay, Gabrielle Rompré, Annie Christine Lajoie, Jason Weatherald, Jean-Christophe Lega, Sébastien Bonnet, Steeve Provencher
Journal: Thorax (2023)

The value placed by patients and their caregivers on the components of composite outcomes in pulmonary arterial hypertension (PAH) remains unknown. We surveyed the importance of these outcomes from a patients’ and caregivers’ perspective, with participants (n=335, including 257 patients with PAH) rating individual components defining clinical worsening in PAH trials as of critical, major, mild-to-moderate or minor importance. Most outcomes were considered of major or mild-to-moderate importance to patients. Death was the only outcome considered of critical importance. Perceptions of clinical outcomes varied between patients and caregivers. Integrating patients’ perception in the elaboration of clinical trials is essential.
European Respiratory Society statement on airway clearance techniques in adults with bronchiectasis
Authors: Beatriz Herrero-Cortina, Annemarie L. Lee, Ana Oliveira, Brenda O'Neill, Cristina Jácome, Simone Dal Corso, William Poncin, Gerard Muñoz, Deniz Inal-Ince, Victoria Alcaraz-Serrano, Gregory Reychler, Angela Bellofiore, Annette Posthumus, Thomy Tonia, James D. Chalmers, Arietta Spinou
Journal: European Respiratory Journal (2023)

Airway clearance techniques (ACTs) are part of the main management strategy for patients with bronchiectasis. Despite being a priority for patients, accessibility, implementation and reporting of ACTs are variable in clinical settings and research studies. This European Respiratory Society statement summarises current knowledge about ACTs in adults with bronchiectasis and makes recommendations to improve the future evidence base. A task force of 14 experts and two patient representatives (10 countries) determined the scope of this statement through consensus and defined six questions. The questions were answered based on systematic searches of the literature. The statement provides a comprehensive review of the physiological rationale for ACTs in adults with bronchiectasis, and the mechanisms of action along with the advantages and disadvantages of each ACT. Evidence on ACTs in clinical practice indicates that the most frequently used techniques are active cycle of breathing techniques, positive expiratory pressure devices and gravity-assisted drainage, although there is limited evidence on the type of ACTs used in specific countries. A review of 30 randomised trials for the effectiveness of ACTs shows that these interventions increase sputum clearance during or after treatment, reduce the impact of cough and the risk of exacerbations, and improve health-related quality of life. Furthermore, strategies for reducing the risk of bias in future studies are proposed. Finally, an exploration of patients’ perceptions, barriers and enablers related to this treatment is also included to facilitate implementation and adherence to ACTs.
Single-nucleus chromatin accessibility identifies a critical role for TWIST1 in idiopathic pulmonary fibrosis myofibroblast activity
Authors: Eleanor Valenzi, Harinath Bahudhanapati, Jiangning Tan, Tracy Tabib, Daniel I. Sullivan, Mehdi Nouraie, John Sembrat, Li Fan, Kong Chen, Silvia Liu, Mauricio Rojas, Audrey Lafargue, Dean W. Felsher, Phuoc T. Tran, Daniel J. Kass, Robert Lafyatis
Journal: European Respiratory Journal (2023)

Background In idiopathic pulmonary fibrosis (IPF), myofibroblasts are key effectors of fibrosis and architectural distortion by excessive deposition of extracellular matrix and their acquired contractile capacity. Single-cell RNA-sequencing (scRNA-seq) has precisely defined the IPF myofibroblast transcriptome, but identifying critical transcription factor activity by this approach is imprecise. Methods We performed single-nucleus assay for transposase-accessible chromatin sequencing on explanted lungs from patients with IPF (n=3) and donor controls (n=2) and integrated this with a larger scRNA-seq dataset (10 IPF, eight controls) to identify differentially accessible chromatin regions and enriched transcription factor motifs within lung cell populations. We performed RNA-sequencing on pulmonary fibroblasts of bleomycin-injured Twist1- overexpressing COL1A2 Cre-ER mice to examine alterations in fibrosis-relevant pathways following Twist1 overexpression in collagen-producing cells. Results TWIST1, and other E-box transcription factor motifs, were significantly enriched in open chromatin of IPF myofibroblasts compared to both IPF nonmyogenic (log 2 fold change (FC) 8.909, adjusted p-value 1.82×10 −35 ) and control fibroblasts (log 2 FC 8.975, adjusted p-value 3.72×10 −28 ). TWIST1 expression was selectively upregulated in IPF myofibroblasts (log 2 FC 3.136, adjusted p-value 1.41×10 − 24 ), with two regions of TWIST1 having significantly increased accessibility in IPF myofibroblasts. Overexpression of Twist1 in COL1A2-expressing fibroblasts of bleomycin-injured mice resulted in increased collagen synthesis and upregulation of genes with enriched chromatin accessibility in IPF myofibroblasts. Conclusions Our studies utilising human multiomic single-cell analyses combined with in vivo murine disease models confirm a critical regulatory function for TWIST1 in IPF myofibroblast activity in the fibrotic lung. Understanding the global process of opening TWIST1 and other E-box transcription factor motifs that govern myofibroblast differentiation may identify new therapeutic interventions for fibrotic pulmonary diseases.
Managing the cancer backlog: a national population-based study of patient mobility, waiting times and ‘spare capacity’ for cancer surgery
Authors: Ajay Aggarwal, Lu Han, Richard Sullivan, Kate Haire, Vijay Sangar, Jan van der Meulen
Journal: The Lancet Regional Health - Europe (2023)

Waiting times for cancer treatments continue to increase in many countries. In this study we estimated potential 'spare surgical capacity' in the English NHS and identified regions more likely to have spare capacity based on patterns of patient mobility (the extent to which patients receive surgery at hospitals other than their nearest).We identified patients who had an elective breast or colorectal cancer surgical resection between January 2016 and December 2018. We estimated each hospital's 'maximum surgical capacity' as the maximum 6-month moving average of its surgical volume. 'Spare surgical capacity' was estimated as the difference between maximum surgical capacity and observed surgical volume. We assessed the association between spare surgical capacity and whether a hospital performed more or fewer procedures than expected due to patient mobility as well as the association between spare surgical capacity and whether or not waiting times targets for treatment were likely to be met.100,585 and 49,445 patients underwent breast and colorectal cancer surgery respectively. 67 of 166 hospitals (40.4%) providing breast cancer surgery and 82 of 163 hospitals (50.3%) providing colorectal cancer surgery used less than 80% of their maximum surgical capacity. Hospitals with a 'net loss' of patients to hospitals further away had more potential spare capacity than hospitals with a 'net gain' of patients (p < 0.001 for breast and p = 0.01 for colorectal cancer). At the national level, we projected an annual potential spare capacity of 8389 breast cancer and 4262 colorectal cancer surgical procedures, approximately 25% of the volumes actually performed.Spare surgical capacity potentially exists in the present configuration of hospitals providing cancer surgery and requires regional allocation for efficient utilisation.National Institute for Health Research.
Opinion: more mouse models and more translation needed for ALS
Authors: Elizabeth M.C. Fisher, Linda Greensmith, Andrea Malaspina, Pietro Fratta, Michael G. Hanna, Giampietro Schiavo, Adrian M. Isaacs, Richard W. Orrell, Thomas J. Cunningham, Abraham Acevedo Arozena
Journal: Molecular Neurodegeneration (2023)

Amyotrophic lateral sclerosis is a complex disorder most of which is 'sporadic' of unknown origin but approximately 10% is familial, arising from single mutations in any of more than 30 genes. Thus, there are more than 30 familial ALS subtypes, with different, often unknown, molecular pathologies leading to a complex constellation of clinical phenotypes. We have mouse models for many genetic forms of the disorder, but these do not, on their own, necessarily show us the key pathological pathways at work in human patients. To date, we have no models for the 90% of ALS that is 'sporadic'. Potential therapies have been developed mainly using a limited set of mouse models, and through lack of alternatives, in the past these have been tested on patients regardless of aetiology. Cancer researchers have undertaken therapy development with similar challenges; they have responded by producing complex mouse models that have transformed understanding of pathological processes, and they have implemented patient stratification in multi-centre trials, leading to the effective translation of basic research findings to the clinic. ALS researchers have successfully adopted this combined approach, and now to increase our understanding of key disease pathologies, and our rate of progress for moving from mouse models to mechanism to ALS therapies we need more, innovative, complex mouse models to address specific questions.